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采用液相色谱-线性离子阱-静电场轨道阱高分辨质谱(LC/LTQ-Orbitrap MS)技术研究候选药物T-VA的裂解规律及体内代谢,建立了大鼠体内T-VA及其代谢产物的LC/MSn分析方法,分析讨论了各自的主要碎片离子峰、质谱特征与结构信息,发现了血浆中主要代谢物M1。借鉴药物化学的方法,合成得到了代谢产物实体M1-1,经1 HNMR、13 CNMR、HRMS确认其结构,根据其色谱、质谱特征进行验证,结果表明,合成得到的M1-1即为血浆主要代谢物M1。借助PC12细胞模型验证了代谢产物M1的神经保护活性,该结果可为进一步研究其生物转化过程与前药修饰提供重要信息。
The cleavage of T-VA and metabolism in vivo were studied by LC / LTQ-Orbitrap MS and T-VA and its metabolites The LC / MSn analysis method was used to analyze and discuss the main fragment ion peaks, mass spectral features and structure information of each fragment, and the main metabolite M1 in plasma was found out. According to the method of medicinal chemistry, the metabolite entity M1-1 was synthesized and confirmed by 1 HNMR, 13 CNMR and HRMS, and its structure was confirmed by its chromatographic and mass spectrometric characteristics. The results showed that the synthesized M1-1 was the main plasma Metabolite M1. The neuroprotective activity of metabolite M1 was verified by PC12 cell model, which could provide important information for further studying its bioconversion process and prodrug modification.